Fluid and electrolytes in pediatrics

CAMPBELL,MD • Professor of Clinical Pediatrics, Albert Einstein College of Medicine, Children’s Hospital at Montefiore, Bronx, NY, USA HOWARDCOREY,MD • Director, Pediatric Nephrology, Go

in Pediatrics

Nutrition and Health

Adrianne Bendich, PhD, FACN, Series Editor

For other titles published in this series, go to

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Children’s Hospital at Montefiore,

Bronx, NY, USA

Leonard G Feld

Department of Pediatrics

Levine Children’s Hospital @

Carolinas Medical Center

Adrianne Bendich, PhD, FACN

GlaxoSmithKline Consumer Healthcare

Parsippany, NJ

USA

Frederick J Kaskel Department of Pediatrics Albert Einstein College of Medicine Children’s Hospital at Montefiore

3415 Brainbridge Ave.

Bronx NY 10467 USA

fkaskel@aecom.yu.edu

ISBN 978-1-60327-224-7 e-ISBN 978-1-60327-225-4

DOI 10.1007/978-1-60327-225-4

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Series Editor Introduction

The Nutrition and Health series of books have, as an overriding mission, to vide health professionals with texts that are considered essential because each includes(1) a synthesis of the state of the science, (2) timely, in-depth reviews by the leadingresearchers in their respective fields, (3) extensive, up-to-date fully annotated referencelists, (4) a detailed index, (5) relevant tables and figures, (6) identification of paradigmshifts and the consequences, (7) virtually no overlap of information between chapters,but targeted, inter-chapter referrals, (8) suggestions of areas for future research, and(9) balanced, data-driven answers to patient /health professionals questions, which arebased upon the totality of evidence rather than the findings of any single study

pro-The series volumes are not the outcome of a symposium Rather, each editor has thepotential to examine a chosen area with a broad perspective, both in subject matter aswell as in the choice of chapter authors The international perspective, especially withregard to public health initiatives, is emphasized where appropriate The editors, whosetrainings are both research and practice oriented, have the opportunity to develop a pri-mary objective for their book, define the scope and focus, and then invite the leadingauthorities from around the world to be part of their initiative The authors are encour-aged to provide an overview of the field, discuss their own research, and relate theresearch findings to potential human health consequences Because each book is devel-oped de novo, the chapters are coordinated so that the resulting volume imparts greaterknowledge than the sum of the information contained in the individual chapters

Of the 31 books currently published in the Series, only four have been given the title

of Handbook These four volumes, (1) Handbook of Clinical Nutrition and Aging, (2) Handbook of Drug-Nutrient Interactions, (3) Handbook of Nutrition and Ophthalmol- ogy, and (4) Handbook of Nutrition and Pregnancy, are comprehensive, detailed and

include extensive tables and figures, appendices and detailed indices that add greatly totheir value for readers Moreover, Handbook contents cut across a wide array of healthprofessionals’ needs as well as medical specialties The Nutrition and Health Series nowwill include its fifth Handbook volume, “Fluid and Electrolytes in Pediatrics: A Com-prehensive Handbook.”

Fluid and Electrolytes in Pediatrics: A Comprehensive Handbook edited by Leonard

G Feld, M.D., Ph.D., M.M.M and Frederick J Kaskel, M.D., Ph.D is a very come addition to the Nutrition and Health Series and fully exemplifies the Series’ goalsfor Handbooks This volume is especially relevant as there is currently no comprehen-sive up-to-date text on the management of fluid and electrolyte disorders in pediatrics.This Handbook provides essential practice guidance that can help to improve the care

wel-of infants and young children in a wide variety wel-of pediatric settings This text, withover 200 relevant tables, equations, algorithms and figures, and close to 1000 up-to-date references, serves as a most valuable resource for the general practitioner, family

vii

practitioner, emergency medicine physicians, residents, medical students, nurses, cian assistants as well as many medical and surgical specialties that care for the disordersseen daily in the children admitted to neonatal intensive care units, pediatric intensivecare units, inpatient units, day hospitals, surgical units, emergency care facilities, andoutpatient care units The Handbook provides detailed instructions about the signs andsymptoms as well as the treatments that can help to restore the fluid balance and pro-tect the vital organs from severe damage that can occur over a matter of hours Healthproviders to the pediatric population who can benefit from the wealth of tables, figuresand formulas as well as the analyses of numerous relevant case studies in the volumeinclude specialties mentioned above as well as endocrinologists, neurologists, clinicalnutritionists, gastroenterologists, neonatologists, emergency room physicians and sup-port staff as well as researchers who are interested in the complexities of maintain-ing fluid and acid–base balance in the preterm, term infant, child and adolescent underacute conditions as well as for those children who have chronic conditions that predis-pose them to fluid and electrolyte imbalances Moreover, graduate and medical students

physi-as well physi-as academicians and medical staff will benefit from the detailed descriptionsthat are provided concerning environmental factors, such as drugs, infections, and otherpotential agents that can cause changes in body fluid balance Tables of normal val-ues for electrolytes, protein, glucose, and other components of the blood are given asdetailed explanations of the compositions of the many fluids that can be provided to thepatient intravenously, or by parenteral, enteral or oral routes in order to return the patient

to normal levels of these essential electrolytes and fluid balance Relevant equations arediscussed and examples of how these can be helpful in treatment choices are illustrated.This text has many unique features, such as highly detailed case studies, that help

to illustrate the complexity of treating the pediatric patient with reduced capability tobalance the body’s fluids There are in-depth discussions of the basic functioning of thekidneys, skin, and the lungs Each chapter describes the etiology and demographics,biological mechanisms, patient presentation characteristics, therapy options and conse-quences of optimal treatment as well as delayed treatment There are also clear, conciserecommendations about fluid intakes, adverse effects of dehydration, and use of drugsand therapies that can quickly improve patient outcomes Thus, this volume provides thebroad knowledge base concerning normal fluid and electrolyte balance, kidney function,cellular physiology and the pathologies associated with changes in fluid balance, and thetherapies that can help to restore normal function

Comprehensive descriptions are provided that concentrate on the importance of ious homeostatic mechanisms that interact with organ systems Diabetes insipidus isreviewed and the differences between central and nephrogenic causes are included aswell as guidance for patient management Individual chapters containing highly relevantclinical examples and background information review the topics of water and sodiumbalance, potassium balance, disorders of calcium, magnesium and phosphorus balance;metabolic acidosis, metabolic alkalosis, respiratory acidosis, and respiratory alkalosis.These chapters include valuable discussions of fetal accretion of electrolytes and theconsequences of preterm birth on fluid balance The final section includes in-depth chap-ters on the consequences of liver disease and ascites, renal failure and transplantation,and endocrine diseases, all of which impact fluid and electrolyte balance There are also

var-chapters that examine genetic diseases, effects of enteral and parenteral nutrition, sequences of excess uric acid and the last chapter contains a comprehensive review ofthe special situations that can arise in the neonatal intensive care unit.

con-The editors of this volume, Dr Leonard G Feld and Dr Frederick J Kaskel areinternationally recognized leaders in the fields of fluid and electrolyte balance and renaldisease research, treatment, and management Dr Feld is the Sara H Bissell and Howard

C Bissell Endowed Chair in Pediatrics, Chief Medical Officer at the Levine Children’sHospital and Clinical Professor of Pediatrics at the University of North Carolina School

of Medicine and Dr Kaskel is the Director of Pediatric Nephrology, Professor and ViceChairman of Pediatrics at Albert Einstein College of Medicine in New York Each hasextensive experience in academic medicine and collectively, they have over 300 peer-reviewed articles, chapters, and reviews and Dr Feld is the editor of the classic volume,

“Hypertension in Children.” Both have been recognized by their peers for their efforts

to improve pediatric medicine especially under conditions where the proper acute carecan have major effects on mortality and/or morbidity for preterm and term neonates,infants, and children The editors are excellent communicators and they have workedtirelessly to develop a book that is destined to be the benchmark in the field of pediatricfluid and electrolyte balance because of its extensive, in-depth chapters covering themost important aspects of this complex field

Fluid and Electrolytes in Pediatrics: A Comprehensive Handbook contains 18

ters and each title provides key information to the reader about the contents of the ter In addition, relevant chapters begin with a list of Key Points, containing conciselearning objectives as well as key words The introductory chapters provide readers withthe basics so that the more clinically related chapters can be easily understood The edi-tors have chosen 26 well-recognized and respected chapter authors who have includedcomplete definitions of terms with the abbreviations fully defined for the reader and con-sistent use of terms between chapters Key features of this comprehensive volume are

chap-the detailed discussions found in chap-the more than 50 case studies In conclusion, Fluid and Electrolytes in Pediatrics: A Comprehensive Handbook, edited by Leonard G Feld and

Frederick J Kaskel provides health professionals in many areas of research and practicewith the most up-to-date, well-referenced volume on the importance of the maintenance

of fluid and electrolyte concentrations in the pediatric population, especially under acutecare This volume will serve the reader as the benchmark in this complex area of inter-relationships between kidney function, and the functioning of all organ systems that areintimately affected by imbalances in total body water Moreover, the physiological andpathological examples are clearly delineated so that practitioners and students can bet-ter understand the complexities of these interactions The editors are applauded for theirefforts to develop the most authoritative resource in the field to date and this excellentHandbook is a very welcome addition to the Nutrition and Health Series

Adrianne Bendich, PhD, FACN

Fluid and Electrolytes in Pediatrics (a comprehensive handbook) is the latest in a

series of multi-authored monographs on the Nutrition and Health Series of books fromSpringer/Humana

Drs Leonard G Feld and Frederick J Kaskel, pediatric nephrologists, and previouscollaborators were selected as the handbook’s editors It was a wise choice, for theyhave each distinguished themselves as exemplary clinicians, investigators, and, mostimportantly, as teachers in this field for over 25 years

A team of 28 experts in all of the topics presented was assembled with thoughtfulconsideration of differing writing styles and perspectives on the subject matter that isoften a function of the author’s depth, breadth, and duration of experience in this field.The editors are to be commended for this approach, which is rarely seen in the manypublications on this general subject over the past 60 years

Chapters 1 and 2 in Part I really “sets the stage” for all that follows, both in terms

of structure/outline and content For this reason, several important features are worthhighlighting:

1 The authors are careful to highlight the critically important differences in the evaluation

of disorders of water and sodium balance

2 To the extent possible, they separate the clinical approaches to both groups of disorderswhile acknowledging the fact that they are inescapably linked This is facilitated by theskillful use of clinical scenarios that the authors work through in a stepwise fashion

3 As a natural consequence of their prior discussion of first principles of sodium and water

physiology, it is particularly noteworthy in Chapter 1 that the dissociation of total body water from total body sodium is illustrated by examples of hyponatremia, isonatremia,

and hypernatremia, each of which may be seen in the context of decreased, normal, orincreased total body water, respectively (e.g., see Figs 6 and 9)

4 The importance of including case scenarios in every one of the chapters underscoresthe time-honored importance of taking a thorough history and performing a completephysical examination; armed with this preliminary information, the astute clinician isusually able to initiate the most appropriate additional diagnostic studies and therapy

The handbook is well organized into the four classical components of any book onthis general subject, starting from the most common to the least common disordersencountered in pediatrics Narratives are clearly expressed, tables and figures were cho-sen to enhance the reader’s understanding of the text, and references seemed manageable

in number and scope

xi

Fluid and Electrolytes in Pediatrics is a handbook worth having now for anyone who

either plans to or is already looking after the health-care needs of all pediatric patients

December 1, 2009

One of the time-honored foundations of the practice of pediatric medicine is theunderstanding and application of the principles of fluid, electrolyte, and acid–base dis-

orders In Fluid and Electrolytes in Pediatrics: A Comprehensive Handbook we have

selected authors with a passion, appreciation of the contributions of pioneers in pediatricmedicine, and an expertise for their respective areas Although medicine has changedenormously from the days of Gamble, Cooke, Holliday, Segar, Winters, and manyother great pediatric clinical investigators, the evaluation and management of fluid, elec-trolyte, and acid–base disorders still form the basis of acute care and inpatient pediatrics.Today pediatric admissions are more complex and the survival of premature infants asyoung as 24 weeks gestation provides challenges for the generalist and specialist alike.Regardless of the location of care – from the neonatal unit, pediatric critical care, inpa-tient service to the emergency rooms – the clinician almost always obtains a set ofelectrolytes and a urinalysis on their patients and must interpret the results with regard

to the specific clinical presentation

In each chapter the authors have provided in-depth discussions, with the assistances ofmany scenarios in order to exemplify the major clinical pearls that will guide our contin-uing understanding and appreciation of the unique characteristics of pediatric fluid andelectrolytes homeostasis We have provided the authors some leeway in placing sce-narios in the text or at the end of the section/chapter In prescribing fluid and electrolytetherapies to our infants, children, and adolescents, we must apply critical analyzing skills

to provide the most precise recommendations in order to assure a safe and effective ronment for our precious future – our children An example is that 5% Dextrose in Waterwith1/2isotonic saline does not work for everyone The jargon of giving 1.5 or 2 times

envi-maintenance fluid therapy is not appropriate because it is the crudest of “estimates.”

In the first section, the chapters on Disorders of Water Homestasis by Feld, gill, and Friedman provide an in-depth examination of hypo- and hypernatremic disor-ders with detailed scenarios supported by many illustrations and tables In the subse-quent chapter on Disorders of Sodium Homeostasis, Woroniecki et al present a discus-sion of sodium balance, renal regulation from the neonatal period, and the approach toassessing renal sodium excretion and the different volume states

Massen-Disorders of Potassium Homeostasis is a key chapter because of the dire quences of abnormal potassium balance and serum concentrations The discussionemphasizes the practical and methodical approach to potassium abnormalities to avoidcatastrophic consequences to the children

conse-In the second section, Charles McKay presents an elaborate review of both Disorders

of Calcium and Magnesium Homeostasis Although calcium disorders with both its lowand high values are quite common, the analysis of the evaluation and treatment withdetailed scenarios helps the reader to achieve a clear understanding of this important

xiii

mineral When faced with an abnormal serum magnesium concentration, this chapterwill be an invaluable resource.

Valerie Johnson presents the chapter on Disorders of Phosphorus Homeostasis with

an exceptional expertise and understanding Similar to magnesium, this chapter is aready resource to assist the clinician in the evaluation, diagnosis, and treatment of phos-phorus disorders

Part III covers Disorders of Acid–Base Homeostasis The section editor Uri Alon hasdone a magnificent job in helping to guide the authors in these five chapters Maheshand Shuster start with an overview of normal acid–base balance, followed by HowardCorey and Uri Alon covering the ever difficult area of metabolic acidosis Their insights

in this field bring a challenging area into simpler terms Wayne Waz reviews metabolicalkalosis and illustrates the value of the “lonely” urine electrolyte – chloride Young andTimmons emphasize the importance of understanding respiratory disorders of acid–basephysiology

Part IV highlights Special Situations of Fluid and Electrolyte Disorders Although

it is nearly impossible to cover all areas, we have tried to include a chapter on theneonatal ICU, liver as well as renal failure, unique situations of the endocrine system,the importance of nutrition and understanding Uric Acid by Bruder Stapleton The bookwould not be complete without a chapter on the genetic syndromes that affect the body’sbalance of water and electrolytes In some instances there is intentional overlap of someinformation in this section to the first three sections of the book

We truly hope that you will find this book an indispensable handbook and guide tothe management of your patients as well as a critical resource for medical and graduatestudents

SPECIAL ACKNOWLEDGEMENT AND THANK YOU

We are truly appreciative for all of the hard work and excellent efforts that were made

by all of the contributing authors The expertise in the preparation of the book is credited

to Richard Hruska, Amanda Quinn and the staff at Humana/Springer Richard was with

us from the inception of this book to the final stages of production A special thanks to

Dr Adrianne Bendich, PhD, for her helpful comments, guidance, and insightfulness inbeing Series Editor of the outstanding Nutrition and Health series

Leonard G Feld, MD, PhD, MMM Frederick J Kaskel, MD, PhD

Dedication v

Series Editor Introduction vii

Foreword xi

Preface xiii

Contributors xvii

P ART I: D ISORDERS OF W ATER , S ODIUM AND P OTASSIUM H OMEOSTASIS 1 Disorders of Water Homeostasis 3

Leonard G Feld, Aaron Friedman, and Susan F Massengill 2 Disorders of Sodium Homeostasis 47

Roberto Gordillo, Juhi Kumar, and Robert P Woroniecki 3 Disorders of Potassium Balance 67

Beatrice Goilav and Howard Trachtman P ART II: D ISORDERS OF C ALCIUM , M AGNESIUM AND P HOSPHORUS H OMEOSTASIS 4 Disorders of Calcium Metabolism 105

Charles P McKay 5 Disorders of Magnesium Metabolism 149

Charles P McKay 6 Disorders of Phosphorus Homeostasis 173

Valerie L Johnson P ART III: D ISORDERS OF A CID –B ASE H OMEOSTASIS 7 Acid–Base Physiology 211

Shefali Mahesh and Victor L Schuster

xv

8 Metabolic Acidosis 221

Howard E Corey and Uri S Alon

9 Diagnosis and Treatment of Metabolic Alkalosis 237

Vani Gopalareddy and Joel Rosh

13 Special Consideration on Fluid and Electrolytes in Acute

Kidney Injury and Kidney Transplantation 301

Oluwatoyin Fatai Bamgbola

14 Adrenal Causes of Electrolyte Abnormalities: Hyponatremia/

Hyperkalemia 315

Lawrence A Silverman

15 A Physiologic Approach to Hereditary Tubulopathies 323

Marva Moxey-Mims and Paul Goodyer

16 Enteral and Parenteral Nutrition 341

Dina Belachew and Steven J Wassner

17 Understanding Uric Acid 355

F Bruder Stapleton

18 Special Situations in the NICU 369

Sheri L Nemerofsky and Deborah E Campbell

Subject Index 395

URIALON, MD • Professor of Pediatrics, Pediatric Nephrology, The Children’s Mercy Hospital Kansas City, MO, USA

OLUWATOYINFATAIBAMGBOLA,MD,FMC(PAED) • Nig, Division of Pediatric Nephrology, Percy Rosenbaum Endowed Professorial Chair in Pediatric

Nephrology, Children’s Hospital of New Oleans, Louisiana State University Health Science Center, New Orleans, LA, USA

DINABELACHEW,MD • Resident in Pediatrics, Penn State Children’s Hospital, The Milton S Hershey Medical Center, Hershey PA, USA

DEBORAH E CAMPBELL,MD • Professor of Clinical Pediatrics, Albert Einstein College of Medicine, Children’s Hospital at Montefiore, Bronx, NY, USA

HOWARDCOREY,MD • Director, Pediatric Nephrology, Goryeb Children’s Hospital, Morristown NJ, USA

LEONARDG FELD,MD, PHD.MMM • Chairman of Pediatrics, Carolinas Medical Center, Chief Medical Officer, Levine Children’s Hospital, Charlotte, NC, USA

AARON FRIEDMAN,MD • Ruben/Bentson Professor and Chair, Department of Pediatrics, University of Minnesota Minneapolis, MN, USA

BEATRICEGOILAV,MD • Assistant Professor of Pediatrics, Albert Einstein College

of Medicine of Yeshiva University Schneider Children’s Hospital, New Hyde Park, New York, USA

PAULGOODYER,MD • Professor of Pediatrics, McGill University Montreal, Quebec, Canada

VANIGOPALAREDDY, MD • Director, Pediatric Liver Transplantation, Levine

Children’s Hospital @ Carolinas Medical Center, Charlotte NC, USA

ROBERTOGORDILLO,MD • Division of Pediatric Nephrology, Children’s Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY, USA

VALERIEL JOHNSON,MD,PHD • Chief, Division of Pediatric Nephrology,

Associate Professor of Clinical Pediatrics Weill Medical College of Cornell

University, Director, Rogosin Pediatric Kidney Center, The Rogosin Institute,

New York, NY, USA

JUHIKUMAR,MD,MPH • Division of Pediatric Nephrology, Children’s Hospital at Montefiore, Albert Einstein College of Medicine, Bronx, NY, USA

SHEFALIMAHESH,MD • Pediatric Nephrology, Children’s Hospital at

Montefiore/Albert Einstein College of Medicine, Bronx, NY, USA

SUSAN MASSENGILL,MD • Director, Pediatric Nephrology, Levine Children’s Hospital @ Carolinas Medical Center, Charlotte NC, USA

xvii

CHARLESMCKAY,MD • Pediatric Nephrology, Levine Children’s Hospital @ Carolinas Medical Center, Charlotte NC, USA

MARVAMOXEY-MIMS,MD • Director, Pediatric Nephrology Program,

NIH/NIDDK/DKUH, Bethesda, MD, USA

SHERIL NEMEROFSKY,MD • Assistant Professor of Pediatrics, Albert Einstein College of Medicine, Children’s Hospital at Montefiore, Bronx, NY, USA

JOELROSH,MD • Director, Pediatric Gastroenterology, Goryeb Children’s Hospital, Morristown, NJ, USA

VICTORL SCHUSTER, MD • Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA

LAWRENCESILVERMAN,MD • Pediatric Endocrinology, Goryeb Children’s

Hospital, Morristown, NJ, USA

BRUDERSTAPLETON,MD • Professor and Chair, Pediatrics, University of

Washington, Chief Academic Officer/Sr Vice President, Seattle Children’s Hospital, Seattle, WA, USA

OTWELLTIMMONS,MD • Pediatric Critical Care, Levine Children’s Hospital @ Carolinas Medical Center, Charlotte, NC, USA

HOWARDTRACHTMAN,MD • Professor of Pediatrics, Albert Einstein College of Medicine of Yeshiva University Schneider Children’s Hospital, New Hyde Park, NY, USA

WAYNEWAZ,MD • Chief, Pediatric Nephrology, Children’s Hospital of Buffalo, Buffalo, NY, USA

STEVENJ WASSNER,MD • Vice Chair for Education, Physician Lead, Children’s Hospital Safety and Quality, Chief, Division of Pediatric Nephrology and

Hypertension, Penn State Children’s Hospital, The Milton S Hershey Medical Center, Hershey, PA, USA

ROBERTWORONIECKI,MD • Division of Pediatric Nephrology, Children’s Hospital

at Montefiore, Albert Einstein College of Medicine, Bronx, NY, USA

EDWINYOUNG,MD • Director, Pediatric Critical Care, Levine Children’s

Hospital @ Carolinas Medical Center, Charlotte, NC, USA

I D ISORDERS OF

1 Disorders of Water Homeostasis

Leonard G Feld, Aaron Friedman, and Susan F Massengill

3 To gain an understanding of the differences between sodium status (which determines the volume

of extracellular volume) and water status (which determines the serum sodium concentration).

4 To recognize clinical signs and symptoms of the different forms of dehydration.

5 To appreciate that the management of hypernatremic dehydration differs from that of isonatremic/hyponatremic dehydration.

Key Words: Hyponatremia; hypernatremia; antidiuretic (ADH); vasopressin; diabetes insipidus; extracellular volume; intracellular dehydration; SIADH; osmolality

1 INTRODUCTION

The disorders of water balance of the body relate to volume control in body fluid

compartments (1) Osmotic shifts of water are directly dependent on the number of

osmotic or solute particles (such as sodium and accompanying anions) that reside within

the membranes of our body fluid compartments (2) The osmolality of the body fluid

compartments (extracellular and intracellular) contributes to the movement of waterthat occurs in a variety of disease states such as gastroenteritis/dehydration An acuteincrease in the extracellular fluid osmolality due to a sodium chloride load results in ashift of water from the intracellular fluid compartment to reduce the osmolality andachieve a new, higher osmolar balance between the two compartments The reversewould occur if there is an acute loss of osmolality from the extracellular fluid com-partment It is simple to appreciate the delicate interaction between osmolality and waterbalance As discussed in Chapter 2, disorders of sodium balance are related to conditionsthat alter extracellular fluid volume (ECF) The simplest example is the requirement tomaintain adequate extracellular volume to sustain perfusion of vital organs and tissues

From: Nutrition and Health: Fluid and Electrolytes in Pediatrics

Edited by: L G Feld, F J Kaskel, DOI 10.1007/978-1-60327-225-4_1,

C

 Humana Press, a part of Springer Science+Business Media, LLC 2010

3

Impairment of tissue perfusion will lead to decreased oxygen delivery and anoxic age resulting in organ failure (i.e., acute renal failure, hepatic failure, brain anoxia) It istherefore necessary to consider the clinical management of disorders of water (osmolal-ity) and sodium balance (ECF volume) collectively The identification and management

dam-of fluid and electrolyte disorders are essential in order to maintain body fluid balance

1.1 Physiology of Water Homeostasis

Maintaining water homeostasis is an essential feature of adaptation for all mammals.Environments rarely provide water in the precise amount and at the precise time needed

A complex set of homeostatic mechanisms are at play, which regulate water intake andwater excretion These include the hypothalamus and surrounding brain, which controlthe sense of thirst and the production and release of arginine vasopressin (AVP), theantidiuretic hormone (ADH) AVP in turn acts on the second important organ in waterhomeostasis – the kidney – leading to increased reabsorption of water by the collectingduct of the kidney

Because of the central role AVP plays in water homeostasis understanding the iologic influences on AVP production and release is important AVP is produced in theparaventricular and supraoptic nuclei, which project into the posterior hypothalamus It

phys-is from the posterior hypothalamus that AVP phys-is released The stimuli that lead to AVPrelease also influence AVP production

The elegant studies performed by Verney established the role of osmolality in the

release of AVP (3) Under normal conditions, it is the osmolality of plasma and

extra-cellular fluid as defined by the extraextra-cellular sodium concentration and associated anionsalong with a small contribution from glucose, which is “sensed” by osmoreceptors inthe anteromedial hypothalamus Small increases in osmolality of 1–2% (increase in2–5 mOsm/kg H2O) will result in the release of AVP Conversely, a similar decrease

in osmolality from approximately 290 to 280 mOsm/kg H2O will result in cessation of

AVP release and decreased production (4).

Non-osmotic stimuli will also cause AVP to be released Gauer and Henry (5)

demon-strated that a reduction in “effective circulating volume” [blood loss, hemorrhage, ECFvolume depletion (dehydration, diuretics, etc.), nephrotic syndrome, cirrhosis, conges-tive heart failure/low cardiac output] will be “sensed” by the pressure or stretch sensi-tive receptors in the left atrium or large arteries of the chest then through the vagus andglossopharyngeal nerve will signal production and release of AVP Other nonosmoticstimuli for AVP secretion include anesthetics and medications, nausea and vomiting,

and weightlessness (6) (Table 1).

AVP circulates unbound, is rapidly metabolized by the liver or excreted by the kidney.The half-life is probably no more than approximately 20 minutes

AVP plays a central role in thirst control Thirst is the drive to consume water toreplace urinary and obligate water losses such as sweating and breathing Thirst is stim-ulated by an increase in serum osmolality and by extracellular volume depletion AVPrelease appears to occur prior to the sensation of thirst, which is about 290 mOsm/Lwith maximal urinary concentration (∼1200 mOsm/L) at about 292–295 mOsm/L.The kidney plays a crucial role in the conservation of water when osmolality isincreased or effective plasma volume is decreased Similarly the kidney can excrete

Table 1

Non-osmotic Stimuli of Physiologic AVP Secretion

Hemodynamic (see text) Non-hemodynamic Medications

Increased Secretion

AcetaminophenBeta-2 agonistsChlorpropamideClofibrateCyclophosphamideEpinephrineLithiumMorphine (high dose)Nicotine

NSAIDsProstaglandinsTricyclic antidepressantsVincristine

Promethazine

NSAID – non-steroidal anti-inflammatory drugs

From Cogan (42); Robertson (43).

water rapidly in response to excess water intake This effect is accomplished by AVPstimulating (1) interstitium through the active transport of urea from the tubule lumen

to the renal epithelial cells of the thick ascending limb of the loop of Henle and thecollecting duct resulting in the development of the osmotic gradient needed to reabsorbwater, and (2) the transepithelial transport of water through opened water channels inthe collecting duct resulting in water reabsorption (Fig 1)

The transepithelial transport of water across the collecting duct (primary site of action

is principle cell) is accomplished by the binding of AVP to its receptor (V2R) onthe basolateral (non-luminal) surface of the epithelial cell The intracellular action ismediated through cyclic AMP and protein kinase A leading to phosphorylation of

aquaporin-2 water channels (7).

Aquaporins are channels that transport solute-free water through cells by permittingwater to traverse cell membranes In the kidney, aquaporin-2 is the channel throughwhich water leaves the lumen of the tubule and enters epithelial cells of the collecting

Fig 1 Countercurrent mechanism for water reabsorption by the nephron Reproduced with

permis-sion from (38, Fig 11.10).

duct Water leaves these same cells through aquaporins-3 and 4 When AVP binds tothe V2R receptor, aquaporin-2, which resides in intracytoplasmic vesicles, is inserted

into the luminal membrane allowing water to move into the cell (8) Aquaporins-3 and

4 appear to reside in the basolateral membranes and facilitate water movement from the

intracellular space into the interstitium (9) This movement of water into the interstitium

is down a concentration gradient The higher solute concentration in the interstitium ofthe kidney is facilitated by the action of AVP on epithelial sodium channels (eNaC) and

the urea transporter (UT-A1) (10, 11).

By 2–3 months of age, the normal infant born at term can maximally concentrateurine to 1100–1200 mOsm/kg H2O similar to an older child or adult AVP has beenmeasured in amniotic fluid and is present in fetal circulation by mid-gestation AVP

levels rise (in fetal sheep) with stimuli such as increased serum osmolality (12) At

birth, vasopressin levels are high but decrease into “normal” ranges within 1–2 days

(13, 14) In neonates, AVP responds to the same stimuli as older children and adults.

However, the ability to concentrate urine to the maximum achieved by older children

or adults does not occur Term infants concentrate up to 500–600 mOsm/kg H2O andpreterm infants up to 500 mOsm/kg H2O These low concentrating levels are probablydue to a number of reasons including decreased glomerular filtration rate, decreasedrenal blood flow, reduced epithelial cell function in the loop of the Henle and collecting

duct, reduced AVP receptor number and affinity and reduced water channel number orpresence on the cell surface Along with decreased renal capacity to reabsorb water,neonates have a reduced capacity to dilute urine so that the range of urine osmolality

in the neonate is between 150 and 500 mOsm/kg H2O as compared to the older child

of 50 and 1200 mOsm/kg H2O Neonates have increased non-urinary water losses (skinand respiratory) as a function of weight, which are greater compared to older childrenand adults The net effect is that neonates are at greater risk of dehydration either due

to inadequate water provision or to high osmolar loads provided in enteral or parenteralfeeds Also, neonates are at greater risk of hyponatremia (hypo-osmolality) if water isadministrated in large quantities or at too rapid rates

2 CLINICAL ASSESSMENT OF RENAL WATER EXCRETION

Under normal conditions the “gold” standard for testing whether water homeostasis

is being maintained is to measure serum and urine osmolality Normal serum ity is approximately 280–290 mOsm/kg H2O As noted above, urine osmolality, except

osmolal-in neonates, can range from 50 to 1200 mOsm/kg H2O and will depend on the iologic circumstances A slight increase in serum osmolytes over a short interval (i.e.,NaCl) will result in AVP release (two- to fourfold increase in circulating concentra-tion of AVP) and a marked increase in water reabsorption and urine osmolality Theconcomitant measurement of an elevated serum osmolality should be matched by anappropriately elevated urine osmolality (>500 mOsm/kg H2O >> the serum osmolal-ity) Likewise, a decrease in serum osmolality, usually the result of water consumption

phys-or other hypotonic solutions, will reduce AVP production and secretion leading to theexcretion of large volumes of water and a lowered urine osmolality A serum osmolalitybelow 280 mOsm/kg H2O should be associated with urine osmolality <250 (often below

200 mOsm/kg H2O) This physiological response depends on an intact hypothalamus–pituitary axis and normal renal function Any stimulus (medications, anesthetics, nau-sea/vomiting) which directly stimulates AVP release, could interfere with normal physi-ologic mechanisms Renal disease, which impairs water delivery to the kidney or affectsloop of Henle or collecting duct function, could impair the response to AVP and lead topathology

Often in clinical situations a quick measure of serum osmolality is the equation

serum osmolality= 2[Na]+[glucose]

2.8where [Na] is the sodium concentration in mEq/L or mmol/L (doubling the sodiumvalue takes into account the accompanying anions – Cl–, HCO3 ); the glucose is mea-sured in mg/dL and the BUN (blood urea nitrogen) in mg/dL The BUN is often omit-ted if it is not rapidly changing since its impact on osmolality is muted by its ability

to move freely across cell membranes By eliminating the BUN term from the tion, the formula is a measure of effective serum osmolality or tonicity Similarly, thespecific gravity on a urine dipstick is used as a quick measure of urine osmolality Aspecific gravity of 1.010 is routinely considered to correlate with a urine osmolality of

equa-300–400 mOsm/kg H2O (multiplying the number to the right of the decimal point by40,000= 0.010 × 40,000 = 400) The higher the specific gravity, the higher the osmo-lality Unfortunately, specific gravity is a crude test that can be affected by solutes such

as albumin (patients with proteinuria have high urinary specific gravity) or glucose Inorder to aid in the diagnosis of diabetes insipidus, direct measurement of osmolality isrequired

2.1 Measurement of the Diluting and Concentrating Ability of the Kidney

The defense of tonicity (effective osmolality) involves the thirst mechanism and theability of the kidneys to excrete or conserve solute-free water depending upon the pres-ence of ADH Urine can be divided into two components One component is the urinevolume containing a solute concentration equal to that of plasma This isotonic com-

ponent has been termed the osmolar clearance (Cosm) and is an index of the kidney’sability to excrete solute particles The second component is the volume of solute-free

water (CH2O) It is this latter volume that effectively changes the osmotic concentration

of the extracellular fluid compartment and is an index of the kidney’s ability to maintain

the serum in an iso-osmolar state (15, 16).

Free-water clearance, abbreviated CH2O, is calculated as shown:

CH2O= ˙V − Cosm,where

Cosm= (Uosm)× ( ˙V)

(Posm)

and where V˙is the urine flow rate (mL/min), Posmis the plasma osmolality, and Uosmis

the urine osmolality

When the kidney reabsorbs equal proportions of water and solute as they exist in the

plasma, the urine has a osmolality equal to plasma, therefore, Cosm = V˙ In this

situa-tion, the osmolality of the ECF remains unchanged When ADH is present or elevated,then solute-free water is reabsorbed in a greater proportion than filtered solute thereby

resulting in a concentrated (hypertonic) urine (Cosm> V˙ ) or a negative C

H2Ovalue Forexample, consider a situation where the urine flow rate is 1 L/day, serum osmolality of

300 mOsm, and urine osmolality of 600 mOsm:

CH2O = 1L/day − (600 mOsm × 1L/day)/300 mOsm

= 1L/day − 2L/day

= −1L/day (or 1L of free water was reabsorbed)

On the other hand, when ADH levels are low, then solute-free water is excreted in agreater proportion than the filtered solute thereby resulting in a dilute (hypotonic) urine

= 0.5L/day free water excreted

Changes in the free-water excretion and reabsorption occur independent of changes

in the solute excretion (Cosm)

2.2 Composition of Body Fluids

As individuals age, the proportion of total body water (TBW) to body weightdecreases Water accounts for 60% of TBW in men and 50% in women while infantshave a higher proportion of water, 70–80%, due to the lower proportion of muscle in

comparison to adipose (17) The higher proportion of TBW to whole body weight in

younger children is mainly due to the larger ECF volume when compared to adults Thedisproportionate weight of brain, skin, and the interstitium in younger children con-tributes to the variability in the ECF volume Water is distributed between two maincompartments, the intracellular fluid compartment (ICF) and extracellular fluid com-partment (ECF) (Fig 2) The intracellular compartment makes up approximately 2/3

TOTAL BODY WATER (TBW)0.6 x Body Weight (BW)

EXTRACELLULAR FLUID

(ECF) 0.2 x BW

INTRACELLULAR FLUID (ICF)

of the TBW The ECF constitutes 1/3 of the TBW composed of plasma and interstitialfluid Abnormal accumulation of plasma ultrafiltrate, also referred to as “third spacedfluids,” can result in edema, ascites, or pleural effusions.

Sodium along with Cl–and HCO3 are the primary determinants of the ECF and vide the osmotic drive to maintain the ECF volume (Fig 3, Table 2) Water moves freelyacross cell membranes between the ICF and ECF compartments to maintain osmotic

Bicarbonate -HCO

Protein and others -P

Phosphates and organic anions -PO

equilibrium For example, an increase in the water content of the ECF causes ment of water into the ICF from the ECF resulting in an expansion of both the ICFand ECF and a new osmolar balance (Fig 4) If extensive, volume overload is clinicallyrecognized as edema, ascites, or pleural effusions In contrast, loss of sodium from theECF results in ECF depletion with some relative ICF expansion and presents as signs ofdehydration (Fig 5) The kidneys are responsible for regulating the water balance andeliminate the majority of water from the body.

AFTER OSMOTIC ADJUSTMENT

AFTER OSMOTIC ADJUSTMENT

Fig 5 Loss of hypertonic fluid and sodium from the ECF secondary to dehydration in a teenager.

Reproduced with permission from Winters (39).

2.3 Maintenance Requirements

For nearly 50 years, we have estimated the caloric and fluid requirements each

day based on the Holliday and Segar method (18) It is based on caloric requirement

each day and the amount of fluid needed based on caloric expenditure (Table 3)

Table 3

Caloric, Water, and Basic Electrolyte Requirements Based on Weight

Body weight (kg) Calories Water

Sodium mEq/100

mL H 2 O

Chloride mEq/100

mL H 2 O

Potassium mEq/100

Water: 100 mL/kg for 1st 10 kg + 50 mL/kg for 5 kg (15–10 kg)= 1250 mL/day

Sodium: 3 mEq/100 mL water= 3 mEq × 12.5 = 36.5 mEq/day or 30 mEq/L of

solution

Potassium: 2 mEq/ 100 mL water= 2 mEq × 12.5 = 25 mEq/day or 20 mEq/L of

solution

The child requires intravenous fluids∼ 1250 mL/day

5% Dextrose with 30 mEq/L of NaCl and 20 mEq/L of KCl at 50 mL/h

5% dextrose is provided to deliver 5 g of carbohydrate per 100 mL of solution or 50 g/L

or 200 calories/L (50 g× ∼4 calories/g of carbohydrate)

NOTE: This solution will only deliver 20% of the daily caloric requirement of 250calories at the maintenance rate For a limited period of time (generally under 5–7 days)this amount of carbohydrate will be sufficient to prevent protein breakdown If it isanticipated that there will be a need for prolonged parenteral therapy, a higher dextrosesolution will be required and provided through a central venous access if the dextroseconcentration in the final solution will exceed 10–12.5%

Recently, a modification to maintenance therapy was proposed substituting isotonic

saline for the hypotonic solution recommended by Holliday and Segar (19) The case

for this modification is based on the observation that some children have been seriouslyinjured [cerebral edema, brain injury and death] by the inappropriate use of maintenancesolutions [hypotonic] especially in situations of unappreciated volume contraction ornonosmotic release of antidiuretic hormone To date, studies regarding the use of iso-tonic saline as maintenance fluid therapy across the full range of hospitalized pediatric

patients are lacking (20).

Intravenous fluids that are safe to administer parenterally based on their osmolalityare shown in Table 4 Each solution is selected based on the clinical status of the patient.Solutions without dextrose (0.45% isotonic saline) or without electrolytes 5% dextrose

in water are only administered under special clinical situations

Table 4

Solutions Used for Intravenous Administration

Solution

Osmolality mOsm/L

Sodium mEq/L

Potassium Eq/L

Chloride mEq/L

Dextrose mOsm/L

∗The lowest intravenous solution that can be used safely is 0.45% isotonic saline with an osmolality

of 154 mOsm/L or approximately 50% of plasma Any solution with an osmolality under this value will result in cell breakdown with a large potassium load to the extracellular space resulting in severe hyperkalemia leading to cardiac arrhythmias and possibly death.

3 HYPONATREMIA AND HYPO-OSMOLALITY

A low serum sodium less than 130 mmol/L (hyponatremia) is nearly always ciated with water retention by the kidney Hyponatremia can occur with extracellularvolume depletion or even extracellular volume expansion such as in the syndrome ofinappropriate antidiuretic hormone (AVP) release or SIADH The presence of elevated

asso-levels of AVP in blood alone does not result in hyponatremia Patients must have an

intake of water or receive a hypotonic solution under the influence of high or sive AVP to become hyponatremic or hypo-osmolar Rarely, hyponatremia is the result

exces-of excessive salt loss Recently an expert panel provided guidelines for hyponatremia

in adults (21) The evaluation and approach to hyponatremia in children is shown in

Fig 6a,b

3.1 Hyponatremic Dehydration

Hyponatremic dehydration is a common condition usually associated with acutegastroenteritis The pathophysiology of this condition involves loss of fluid andelectrolytes in stool (sodium, bicarbonate, water usually hypo-osmolar to extracellularfluid) and emesis This extrarenal loss results in extracellular volume depletion lead-ing to the release of aldosterone and the non-osmotic release of AVP Aldosterone willincrease renal sodium reabsorption with a loss of urinary potassium eventually leading

to hypokalemia AVP will increase water reabsorption, and if the extracellular volumedepletion is allowed to persist with the patient provided hypo-osmolar fluids either bymouth (clear liquids) or intravenously (5% dextrose + 0.225 (1/4) isotonic saline or 5%dextrose + 0.45 (1/2) isotonic saline), the patient develops a hypo-osmolar or hypona-tremic state

With advances in biochemical

techniques these issues rarely exist

or hypertonic glucose

To calculate correction calculation for sodium (For each 100 mg/dL increase in the serum glucose concentration, the serum [Na] decreases by ~ 1.6 mEq/dL)

To calculate correction calculation for sodium (For every 0.5 gm/kg of mannitol given, the serum [Na] decreases by 4–5

mEq/L)

Treat underlying condition

Step 1: Rule out pseudohyponatermia or

hypertonic hyponatremia

Fig 6 Suggested evaluation of hyponatremia based on plasma osmolality or tonicity Modified with

permission from Feld (40).

(Continued)

Fig 6 (Continued)

The signs and symptoms of hyponatremic dehydration are primarily those of dration Table 5 describes the generally accepted clinical signs and symptoms ofdehydration as a percent of body weight lost In general, with hyponatremia (hypo-osmolality) the symptoms/signs are more pronounced than the actual percent ofbody weight lost This occurs because the extracellular fluid space is more signifi-cantly impacted than in iso-osmolar (normal serum sodium) or hyperosmolar (hyper-natremic) dehydration If the serum sodium falls rapidly (>10 mEq/L per 24 h)

dehy-or decreases below 125 mEq/L, the patient may experience mdehy-ore significant tral nervous system symptoms – more profound lethargy, obtundation, and seizures.Seizures associated with hyponatremia are more refractory to treatment with antiepilep-tics and requires an increase in serum osmolality or reversal of the hypo-osmolality(hyponatremia)

cen-The approach to hyponatremic dehydration involves treatment of the underlying dition, administration of oral or intravenous therapy to correct the dehydration and directtreatment of the hyponatremia, if necessary (Scenario 1) For mild to moderate dehy-dration providing oral restoration usually is sufficient unless vomiting is frequent andthere is lack of evidence that fluids consumed in a therapeutic fashion (5–15 mL every

9% = shock)

(<1 mL/kg/h)

Oliguria

decreasedCool, mottling,

Infants < 12 months of age

Reproduced with permission from Feld (41).

Table 6

Restoration Oral Solutions

Restoration (rehydration) oral solutions Solution Carbohydrate g/L Na mmol/L K mmol/L

Osmolality mOsm/kg H 2 O

5–10 min) would be retained Tables 6 and 7 describe commonly used oral and venous restoration (rehydration) fluids For moderate dehydration, the World HealthOrganization recommends oral rehydration solutions However, many clinicians will ini-tiate intravenous treatment followed by oral therapy The restorative, intravenous treat-ment for extracellular volume depletion is isotonic saline (normal saline) For moderate

intra-to severe dehydration, an intravenous bolus of 20–40 mL/kg of isointra-tonic saline should

be provided over 30–60 min depending on the clinical state (more rapid administration

Table 7

Intravenous Restoration (Rehydration) Solutions

Solution Na mmol/L K mmol/L Cl mmol/L Ca mmol/L

Lactate mmol/L

in patients with hypotension, decreased turgor or tachycardia) The vast majority ofpatients will improve and the institution of oral fluids can be started With improve-ment in extracellular volume depletion in patients with gastroenteritis, gut perfusion

improves and oral rehydration is better tolerated (22) This approach will not only restore

extracellular volume but allow the serum sodium concentration to approach normalvalues

Case Scenario 1 Hyponatremia with Sodium and Water

Deficits = Hypovolemia

A 4-month-old infant presents to her pediatrician with a 4–5 day history of low-gradefever (38–38.5◦C), numerous watery diarrhea, and decreased activity Since the childrefused to take her usual breast milk volume or solid foods, the mother and grandmothersubstituted non-carbonated soda (coca-cola, ginger ale, apple juice, or orange juice willhave∼550–700 mOsm/kg H2O with less than 5 mEq/L of sodium) and “sweet” (sugar-added) iced tea Over the last 12 h there were a few episodes of emesis and there wereless wet diapers

On examination the child was lethargic, dry mucous membranes, no tears, sunkeneyeballs, and reduced skin turgor Vitals signs were the following: blood pressure74/43 mmHg, temperature of 38◦C, respiratory rate of 36/min, and pulse of 175beats/min The weight was 6 kg Weight at the time of her immunization 7 days agowas 6.6 kg There were no other significant findings

With the magnitude of dehydration and lethargy, the decision by the clinician was

to initiate parenteral fluid replacement rather than oral rehydration therapy The childwas admitted to the hospital with diagnosis of dehydration On admission the laboratorystudies were as follows:

Sodium 124 mEq/L, chloride 94 mEq/L (normal 98–118 mEq/L), potassium 4 mEq/L mal 4.1–5.3 mEq/L), bicarbonate (or total COs) 12 mEq/L (normal 20–28 mEq/L ormmol/L), serum creatinine 0.8 mg/dL (normal ∼0.3–0.5 mg/dL), blood urea nitrogen

(nor-40 mg/dL, blood glucose 70 mg/dL; complete blood count was normal except for a tocrit of 38% (normal∼36%);

hema-Urinalysis/chemistries: specific gravity of 1.030, trace protein, no blood or glucose, smallketones; urine creatinine 40 mg/dL and sodium 15 mEq/L

Fractional excretion of sodium (FENa)

([urine sodium× serum creatinine]/[serum sodium × urine creatinine] × 100% ) =

([15 mEq/L × 0.8 mg/dL]/[129 mEq/L × 40 mg/dL]) = 0.23%

Normal values for FENa= ∼ 1 − 2% ; decreased renal perfusion

(dehydration, decreased intravascular volume) < 1%

3.2 Assessment

The clinical and laboratory information suggest hyponatremic dehydration secondary

to extrarenal losses from diarrhea with administration by the family of hypotonic ordilute fluids The child has lost proportionally more sodium than water or a relativelyhypertonic fluid loss The result is a lower extracellular fluid osmolality compared to the

intracellular fluid osmolality The magnitude of the dehydration is about 10% or ate to severe The pre-illness weight was 6.6 kg with a current weight of 6 kg or a 0.6 kg

moder-loss over the last week Estimated guidelines for vital signs at this age: the normal ratory rate for children is approximately 36; normal pulse is about 130 (standard devia-tion is∼45) beats/min; normal blood pressure is approximately 89/54 mmHg As notedabove, the decision by the clinician was to initiate parenteral fluid replacement ratherthan oral rehydration therapy The relative contraindications for oral rehydration ther-apy would include a young infant less than 3–4 months of age, the presence of impend-ing shock or markedly impaired perfusion (increased capillary refill time/decreased skinturgor), inability to consume oral fluids due to intractable vomiting, marked irritability

respi-or lethargy/unresponsiveness respi-or the judgment of the clinician

Emergent or acute phase – Over about 1 h (this may need to be prolonged in cases of

more significant volume depletion) In order to re-establish circulatory volume to vent prolonged loss of perfusion to the key organs such as kidney, brain, gastrointestinaltract, the fluid choices would be isotonic (0.9%) saline (normal saline) or another iso-tonic/hypertonic solution such as 5% albumin, Ringer’s lactate, or a plasma preparation.With the availability of isotonic saline, this is the usual fluid choice

pre-Weight (kg)× fluid bolus of 20 mL/kg over 30–60 min

(If the patient was in shock the fluid delivery would be a more rapid infusion to preventorgan failure.)

6 kg× 20 mL = 120 mL over 30–60 min This only replaces 20% of the losses [total losses

600 mL]

Acute – Repletion/Replacement/Restoration Phase – Over 24 h; in this period the

daily fluid/electrolyte maintenance requirements and deficit calculation are derived fromstandard estimates

1 Maintenance fluid/electrolyte calculations for 24 h:

Calculations based on daily caloric requirements.

Electrolyte needs mEq/100 calories used per day (alternate method

is mEq/kg per day)

Calories derived from glucose/dextrose

2.5–3 mEq (or

3 mEq/kg)Potassium=

2–2.5 mEq(or∼ 2 mEq/kg)

5 g/100 caloriesused

∗Kidney losses are about 45–75 mL/100 calories expended; sweat losses usually 0; stool losses

are about 5–10 mL/100 calories expended, and insensible losses (skin ∼30 mL + respiratory

∼15 mL ) are about 45 mL/100 calories expended – 100 mL of total daily water losses = 100

calories expended per day or 1 mL = 1 calorie.

For this 6.6 kg infant

Maintenance requirements for 24 h

Potassium 2 mEq/100 mL× 660 mL = 13 mEq

2 Deficit Replacement of water and electrolytes: In most circumstances the acid–base

dis-order is a simple metabolic acidosis that does not require bicarbonate replacement unlessthere is severe tissue/impaired circulatory compromise such as shock (generally 15%dehydration) In general, there is only partial replacement of potassium deficits that arefully corrected over 2–4 days following resumption of oral intake

There are two approaches to calculate deficits in hyponatremic dehydration

Approach 1: Use of the table below for 10% dehydration

Type of dehydration∗

based on serum [Na] in mEq/L Water (mL/kg)

Sodium (mEq/kg)

Potassium (mEq/kg)

∗Isonatremic dehydration is the most common accounting for 70–80% of infants and children;

hypernatremic dehydration accounts for about 15%, and hyponatremic dehydration for about 5–10%

of cases Adapted from Winter RW: Principles of Pediatric Fluid Therapy, 2nd Ed, Little Brown and Co., Boston, 1982, p 86.

For this 6 kg infant with hyponatremic dehydration at 10%

Deficits for 24 h

Water Pre-illness weight – Illness weight= 6.6–6 kg = 0.6 kg = 600 mLSodium 10 mEq× 6.6 kg = 66 mEq

Potassium 8 mEq× 6.6 kg = 53 mEq

Total First 24 h Requirements

The total amount of maintenance and deficit amounts are given 50% over the first 8 hand the remainder over the next 16 h

Component of

Hourly rate Round number up or down to the nearest

864343

663333

72 mL/h

36 mL/h

• From clinical experience the gastrointestinal losses tend to resolve or decrease cantly following the initiation of parenteral therapy If it does continue these losses willneed to be added to the ongoing loss row

signifi-• For each liter of IV solution there would be 43 mEq/0.58 L= ∼75 mEq/L for the 1st 8 h,

then about 35 ml/h for the next 16 h

• Fluid selection – 5% dextrose + 0.45% isotonic saline + 40 mEq KCl/L

Generally the final solution potassium concentration is about 30– 40 mEq/L (it should not exceed 40 mEq/L without close intensive care monitoring) Some clinicians have

recommended using a lower concentration of 20–25 mEq/L since potassium stores will

be replenished when the child restart oral feeds The 5% dextrose provides 50 g ofcarbohydrate per liter of 50 g× ∼4 calories/g = 200 calories This would be about 20%

of the daily caloric intake which is sufficient to prevent protein breakdown over a shorttreatment period (less than 1 week)

Approach 2: Direct Deficit Calculation

a Sodium deficit: Fluid deficit (L) × 0.6 (sodium distribution factor) × normal serum

sodium concentration= 0.6 L × 0.6 × 140 mEq/L = 50 mEq

b Additional sodium= (Desired serum sodium – actual serum sodium) × 0.6 L/kg × kg

body weight= (135 – 124 mEq/L) × 0.6 L/kg × 6.6 kg = 43.6 mEq∗

c Total sodium deficit= 50 + 43.6 = 94 mEq

d Total potassium deficit= Fluid deficit (L) × 0.4 (potassium distribution factor) × normal

intracellular potassium concentration= 0.6 L × 0.4 × 120 mEq/L = ∼ 29 mEq

• In cases of isonatremic dehydration, the calculation is identical except the additionalsodium deficit (b above) is excluded from the calculation

Total First 24 h Requirements

The maintenance is provided equally over the entire 24 h period, and deficit amountsare given 50% over the first 8 h (emergent phase is usually excluded from the 24 hcalculations) and the remainder over the next 16 h

Component of therapy Water Sodium Potassium

Hourly rate Round number

up or down to the nearest 5 increment

× 0.12 L)

0 Entire amount

over20–60 min

• For the first 8 h, each liter of IV solution there would be 64 mEq/0.52 L= 123 mEq of

sodium per liter= Fluid selection – 5% dextrose + isotonic saline + 40 mEq KCl/L at a

rate of 520 mL/7 h = ∼75 mL/h

• For the remaining 16 h, each liter of IV solution there would be 71 mEq/0.74 L =

95 mEq/L = Fluid selection – 5% dextrose + 0.45% isotonic saline + 40 mEq KCl/L

at a rate of 740 mL/16 h = ∼45 mL/h

The major difference in the two approaches is the provision of isotonic saline rather

1/2 isotonic saline in the first 8 h Thereafter, the approaches are nearly identical Asstated above, using a lower intravenous potassium concentration of 20–25 mEq/L isalso acceptable

Signs and symptoms (Fig 6b) attributable to hyponatremia include anorexia, ness, lethargy, confusion, seizures, and coma It seems appropriate here to point out thatalthough hyponatremia is not unusual, the central nervous system (CNS) manifestationsare fortunately quite uncommon What protects the CNS from swelling whenever theosmolality falls (in situations of hyponatremia or in situations of decreasing osmolalitywhen the serum osmolality starts above normal such as the correction of hypernatremia)

weak-are at least 5 physiological process recently reviewed by Chesney (23) These processes

include diminished ADH secretion unless volume contraction exists simultaneously;reduced movement of brain cell aquaporins (aquaporin-4) thus reducing water move-ment into brain cells; movement of ionic and nonionic osmolytes out of cells especially

in the brain; existing mechanisms that regulate cell volume; and existing mechanismsthat sense intracellular osmolality The interchanges between these processes help keepthe brain from swelling when the osmolality falls but they can be overwhelmed whenthe rate of water ingested by the patient or infused into the patient exceeds these regula-tory controls However, in situations with significant neurological symptoms (seizures,coma) associated with hyponatremia, a more rapid increase in the serum sodium andosmolality needs to be considered Under those conditions, the use of a hypertonicsalinesolution may be necessary Three percent NaCl (500 mEq NaCl/L – 0.5 mEq/mL) is

the preferred solution The recommended change in serum sodium should not exceed

10 mEq/L/24 h (approximately 20 mOsm/kg H2O/24 h – Na and Cl each contributes

10 mOsm/kg H2O) To calculate the amount of sodium required to change the serumsodium concentration, the following equation can be used:

(Desired [Na]− Measured [Na]) × BW × 0.6EX: To raise the serum sodium concentration from 123 to 130 mEq/L for a 10 kgchild – (130–123)× 10 kg × 0.6 = 42 mEq

[Na] is the sodium concentration in mEq (or mmol/L) BW is bodyweight in grams and 0.6 represents the 60% of BW (except newborns and young neonates) that

kilo-is water The entire body water space kilo-is used for thkilo-is calculation since sodium added

to the extracellular space raises extracellular (ECF) osmolality drawing water from theintracellular space into the extracellular to equalize osmolality in the body fluid com-partments In most patients, 3% saline correction is only administered until symptomsare abated which usually occurs when the serum sodium is raised by approximately5–10 mEq (osmolality – 10–20 mOsm/kg H2O) Ultimately, patients can be cor-rected near the lower limit of the normal range for serum sodium – approximately

130 mEq/L An infusion 6 mEq/kg/h (there is 0.5 mEq/mL in the 3% NaCl solution

which implies a delivery volume of 12 mL/kg/h) of a 3% NaCl solution will raise theserum sodium approximately 5 mEq/h.

3.4 Syndrome of Inappropriate Antidiuretic Hormone (SIADH) Release

In the classic description by Bartter and Schwartz, SIADH release includes tremia and hypo-osmolality of the serum, a urine osmolality that is inappropriatelygreater than serum, normal renal, thyroid and adrenal function and increased urine

hypona-sodium excretion (24) Another way to view SIADH release is as a non-physiologic

condition of AVP excess Thus release of AVP due to hyperosmolality or volume tion does not represent inappropriate ADH release because both represent physiologicrelease of AVP So SIADH cannot occur in a state of negative water balance SIADHrelease can be viewed as having three basic causes – (a) ectopic production, (b) exoge-nous administration of vasopressin, or (c) “abnormal” release of AVP from neurohy-pophysis Table 8 lists some of the more common causes of SIADH release

deple-In SIADH AVP is released despite a normal or low serum osmolality As notedabove, the excess AVP results in a further reduction in serum sodium and osmolalityonly if the patient continues to consume water in excess to urine and insensible losses(sweating and respiration) Because patients are not volume depleted (in fact they arevolume expanded), urinary sodium losses are high SIADH release is associated withtotal body water expansion; high urine sodium concentration without evidence of heart,liver, or kidney diseases; and no edema The diagnostic criteria for SIADH are listed inTable 9

The treatment of choice for SIADH release is to treat the underlying cause such

as a direct therapy for ectopic AVP production, removal of an offending drug agent;

or reduction in the dose or lengthening the interval of exogenous AVP administration.Since treatment of the underlying cause may not be possible, fluid restriction is ofteneffective The total fluid intake should be less than that excreted in urine and from insen-sible loss (approximately 40% of maintenance calculation) This therapy will raise theserum sodium by 2–3 mEq/L/24 h Other proposed therapies for a more rapid increase

in sodium (osmolality) include (a) doxycycline, a tetracycline derivative that interfereswith the action of AVP but cannot be used in young children, (b) fludrocortisone, whichincreases sodium retention but leads to hypokalemia and hypertension, and (c) AVPantagonists AVP antagonists appear effective in short-term trials but are untested in

children (25) Finally, prevention of hyponatremia by limiting water intake in situations

where one might expect SIADH to occur, such as neurological surgery, is warranted

Case Scenario 2 Patient with Meningitis and SIADH

A 10-month-old infant presents to the pediatric emergency room with a generalizedtonic clonic seizure The child had a fever to 39–40◦C for the past 24–36 h, lethargy,

vomiting, decreased oral intake, and less wet diapers The child did not receive Prevnar(pneumococcal vaccine)

On examination the child appeared ill and irritable resisting any movement Vitalssigns were the following: blood pressure 94/58 mmHg; temperature of 39◦C, respira-

tory rate of 40/min, and pulse of 175 beats/min The weight was 10 kg There were no